Abstract Text: Oral lichen planus (OLP) is a chronic inflammatory mucosal disease that involves band-like infiltration of activated T cells and liquefactive degeneration of basal epithelial cells. Our previous study has shown abundant bacterial infection within the epithelium and lamina propria of OLP lesions. This study aimed to investigate the hypothesis that bacterial antigens can be presented to CD4+ T cells by oral keratinocytes, leading to liquefactive degeneration. To demonstrate this, we used immortalized mouse oral keratinocytes (IMOK), OTII peptide-expressing E. coli 7.2 (a strain isolated from an OLP tissue) and OTII-specific CD4+ T cells. First, we confirmed that E. coli stained with pHRodo invades keratinocytes. We examined the expression of the molecules required for interaction with CD4+ T cells, including MHC class II, CD40 and ICAM-1, on IMOK cells. While ICAM-1 was upregulated both by IFNγ and E. coli infection, MHC class II was only induced by IFNγ, and CD40 expression required synergistic effect of IFNγ and E. coli infection. The OTII CD4+ T cells obtained from transgenic mice were differentiated into Th1/Th17 cells using polarizing cytokines. The polarized OTII Th1/Th17 cells were activated by IMOK cells pulsed with OTII peptide. When OTII Th1/Th17 cells and IMOK infected with OTII-expressing E. coli were cocultured, Th1 cells effectively cleared intracellular E. coli, while Th17 cells were able to rescue IMOK from cell death induced by IFNγ and E. coli. This study will help understand the interplay of infected keratinocytes and Th1/Th17 cells in the pathogenesis of OLP.
